In these studies, we will continue efforts to answer specific questions concerning the metabolic effects of certain drugs which act on the central nervous system and by this means to work toward statements about the mechanisms by which these agents exert their pharmacological influences. To do this, we will utilize recently developed optical techniques for continuously and noninvasively monitoring oxidative metabolism in intact brain tissues of animal models previous to, during and following drug administrations. Although there are well known behavioral effects of CNS-active agents, efforts at determining the basis for neurochemical and electrophysiological changes have been inconclusive for many categories of drugs. Experiments in our laboratory under this program have led to the conclusion that cerebral and spinal cord metabolism are under different controls than is expected from in vitro extrapolation of mitochondrial activity and that studies on intact tissues will be required to solve complex problems of CNS pharmacology. In the proposed investigations, redox changes in intramitochondrial NADH will be monitored by microfluorometry and the technique of reflection spectrophotometry will measure redox changes in the cytochromes together with changes in hemoglobin ozygenation state and blood volume. Simultaneously, we will complete the development of the computer-assisted "rapid scanning fluorospectrophotometer" to measure all of these parameters at one time. By correlating these parameters of oxidative metabolism with electrophysiological activities, we will record how pharmacological interventions alter patterns of tissue activity. Further work along this line may well yield significant new insights into the energy metabolism of the brain and on the action of CNS drugs.